Chromosome segregation analysis in human embryos obtained from couples involving male carriers of reciprocal or Robertsonian translocation

Abstract

The objective of this study was to investigate the frequency and type of chromosome segregation patterns in cleavage stage embryos obtained from male carriers of Robertsonian (ROB) and reciprocal (REC) translocations undergoing preimplantation genetic diagnosis (PGD) at our reproductive center. We used FISH to analyze chromosome segregation in 308 day 3 cleavage stage embryos obtained from 26 patients. The percentage of embryos consistent with normal or balanced segregation (55.1% vs. 27.1%) and clinical pregnancy (62.5% vs. 19.2%) rates were higher in ROB than the REC translocation carriers. Involvement of non-acrocentric chromosome(s) or terminal breakpoint(s) in reciprocal translocations was associated with an increase in the percent of embryos consistent with adjacent 1 but with a decrease in 3∶1 segregation. Similar results were obtained in the analysis of nontransferred embryos donated for research. 3∶1 segregation was the most frequent segregation type in both day 3 (31%) and spare (35%) embryos obtained from carriers of t(11;22)(q23;q11), the only non-random REC with the same breakpoint reported in a large number of unrelated families mainly identified by the birth of a child with derivative chromosome 22. These results suggest that chromosome segregation patterns in day 3 and nontransferred embryos obtained from male translocation carriers vary with the type of translocation and involvement of acrocentric chromosome(s) or terminal breakpoint(s). These results should be helpful in estimating reproductive success in translocation carriers undergoing PGD.

Figure 1. Chromosome segregation in day 3 cleavage stage and spare embryos obtained from male translocation carriers^a.

^aREC = reciprocal translocation; ROB = Robersonian translocation, N/B = chromosomally normal or balanced for the translocated chromosomes, Adj1 = adjacent 1, Adj2 = adjacent 2, NS = no known segregation pattern detected, Poly = polyploid. An asterisk (*) denotes statistically significant differences (P<0.05). The column labeled with “3∶1” represents frequency of 3∶0 segregants in ROB and 3∶1 in REC. Normal/balanced spare embryos in ROB and REC carriers were not compared.